PMID- 34728779
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20230207
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Nov 2
TI  - A pre-formulation study of tetracaine loaded in optimized nanostructured lipid 
      carriers.
PG  - 21463
LID - 10.1038/s41598-021-99743-6 [doi]
LID - 21463
AB  - Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal 
      blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid 
      carriers (NLC) may prolong TTC delivery at the site of injection, reducing such 
      toxicity. This work reports the development of NLC loading 4% TTC. Structural 
      properties and encapsulation efficiency (%EE > 63%) guided the selection of three 
      pre-formulations of different lipid composition, through a 2(3) factorial design 
      of experiments (DOE). DLS and TEM analyses revealed average sizes (193-220 nm), 
      polydispersity (< 0.2), zeta potential |- 21.8 to - 30.1 mV| and spherical shape 
      of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on 
      their structure and physicochemical stability over time. Interestingly, one 
      optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, 
      as predicted by Raman imaging that detected lack of miscibility between its solid 
      (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified 
      lamellar arrangements inside such nanoparticles, the thickness of the lamellae 
      been decreased by TTC. As a result of this combined approach (DOE and biophysical 
      techniques) two optimized pre-formulations were rationally selected, both with 
      great potential as drug delivery systems, extending the release of the anesthetic 
      (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells.
CI  - (c) 2021. The Author(s).
FAU - Castro, Simone R
AU  - Castro SR
AD  - Department of Biochemistry and Tissue Biology, Institute of Biology, University 
      of Campinas (UNICAMP), Rua Monteiro Lobato 255, Campinas, SP, 13083862, Brazil.
FAU - Ribeiro, Ligia N M
AU  - Ribeiro LNM
AD  - Department of Biochemistry and Tissue Biology, Institute of Biology, University 
      of Campinas (UNICAMP), Rua Monteiro Lobato 255, Campinas, SP, 13083862, Brazil.
AD  - Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, 
      Brazil.
FAU - Breitkreitz, Marcia C
AU  - Breitkreitz MC
AD  - Department of Analytical Chemistry, Institute of Chemistry, UNICAMP, Campinas, 
      SP, Brazil.
FAU - Guilherme, Viviane A
AU  - Guilherme VA
AD  - Department of Biochemistry and Tissue Biology, Institute of Biology, University 
      of Campinas (UNICAMP), Rua Monteiro Lobato 255, Campinas, SP, 13083862, Brazil.
FAU - Rodrigues da Silva, Gustavo H
AU  - Rodrigues da Silva GH
AD  - Department of Biochemistry and Tissue Biology, Institute of Biology, University 
      of Campinas (UNICAMP), Rua Monteiro Lobato 255, Campinas, SP, 13083862, Brazil.
FAU - Mitsutake, Hery
AU  - Mitsutake H
AD  - Department of Analytical Chemistry, Institute of Chemistry, UNICAMP, Campinas, 
      SP, Brazil.
FAU - Alcantara, Ana C S
AU  - Alcantara ACS
AD  - Department of Chemistry, Federal University of Maranhao, Sao Luis, MA, Brazil.
FAU - Yokaichiya, Fabiano
AU  - Yokaichiya F
AD  - Department of Quantum Phenomena in Novel Materials, Helmholtz-Zentrum, Berlin, 
      Germany.
FAU - Franco, Margareth K K D
AU  - Franco MKKD
AD  - Nuclear and Energy Research Institute, IPEN-CNEN/SP, Sao Paulo, SP, Brazil.
FAU - Clemens, Daniel
AU  - Clemens D
AD  - Department of Quantum Phenomena in Novel Materials, Helmholtz-Zentrum, Berlin, 
      Germany.
FAU - Kent, Ben
AU  - Kent B
AD  - Department of Quantum Phenomena in Novel Materials, Helmholtz-Zentrum, Berlin, 
      Germany.
FAU - Lancellotti, Marcelo
AU  - Lancellotti M
AD  - Faculty of Pharmaceutical Sciences, UNICAMP, Campinas, SP, Brazil.
FAU - de Araujo, Daniele R
AU  - de Araujo DR
AD  - Human and Natural Science Center, Federal University of ABC (UFABC), Santo Andre, 
      SP, Brazil.
FAU - de Paula, Eneida
AU  - de Paula E
AD  - Department of Biochemistry and Tissue Biology, Institute of Biology, University 
      of Campinas (UNICAMP), Rua Monteiro Lobato 255, Campinas, SP, 13083862, Brazil. 
      depaula@unicamp.br.
LA  - eng
GR  - S.R.C. fellowship/FAPEAM/
GR  - 14/25372-0/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
GR  - 14/14457-5/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211102
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Anesthetics, Local)
RN  - 0 (Drug Carriers)
RN  - 0619F35CGV (Tetracaine)
SB  - IM
MH  - Anesthetics, Local/chemistry/*pharmacology
MH  - Animals
MH  - BALB 3T3 Cells
MH  - *Cell Proliferation
MH  - Drug Carriers/*chemistry
MH  - Drug Compounding/*methods
MH  - *Drug Liberation
MH  - Mice
MH  - Nanostructures/*administration & dosage/chemistry
MH  - Tetracaine/chemistry/*pharmacology
PMC - PMC8563806
COIS- The authors declare no competing interests.
EDAT- 2021/11/04 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/11/02
CRDT- 2021/11/03 06:48
PHST- 2021/03/23 00:00 [received]
PHST- 2021/09/30 00:00 [accepted]
PHST- 2021/11/03 06:48 [entrez]
PHST- 2021/11/04 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/11/02 00:00 [pmc-release]
AID - 10.1038/s41598-021-99743-6 [pii]
AID - 99743 [pii]
AID - 10.1038/s41598-021-99743-6 [doi]
PST - epublish
SO  - Sci Rep. 2021 Nov 2;11(1):21463. doi: 10.1038/s41598-021-99743-6.